Soluble P-selectin as a marker of in vivo platelet activation.

BACKGROUND: Platelets are the major source of circulating sP-selectin. Elevated levels of this protein have been found in many atherothrombotic disorders. Thus, we investigated whether sP-selectin dosage might reflect platelet function in patients with risk factors for or with established cardiovascular diseases and whether its levels can be modulated by aspirin therapy. METHODS: Plasma sP-selectin levels and light transmission platelet aggregometry (LTA) were analyzed in 152 outpatients. The effects of a 6-month aspirin therapeutic course on sP-selectin levels and LTA in 51 consecutive patients have been also investigated. RESULTS: Significant correlations were observed between sP-selectin and Mx% LTA in response to epinephrine (p=0.022) and arachidonic acid (p=0.006), or between sP-selectin and collagen lag-phase (p=0.016). Multiple regression analysis showed that the only predictors of sP-selectin levels were platelet number (p<0.001) and collagen-induced lag-phase (p<0.01). Aspirin-treated patients showed a significant reduction of sP-selectin levels by 13% (p=0.021) which significantly correlated with collagen-induced lag-phase (p=0.005). CONCLUSIONS: sP-selectin dosage could be proposed as a reliable marker of platelet activation in patients with major atherosclerotic risk factors either in the absence of clinically overt disease, and might represent a valid tool to asses in vivo platelet behavior.

In vivo platelet activation is responsible for enhanced vascular endothelial growth factor levels in hypertensive patients.

BACKGROUND: Essential hypertension may be a consequence of an abnormal regulation of vascular endothelial growth factor (VEGF). In vivo activation of platelets does result in the release of VEGF. Thus, we investigated whether VEGF production in hypertensive patients is related to in vivo platelet activation, and whether it may be modified by aspirin treatment. METHODS: Plasma VEGF, soluble (s)P-selectin and thrombin-anti-thrombin complex (TATc) were analyzed in 80 patients with therapeutically controlled essential hypertension and 40 age and sex-matched healthy normotensive controls. The effects of a 6-month treatment with aspirin 100 mg/day on VEGF levels of 20 hypertensive patients were also studied. RESULTS: Plasma VEGF (p<0.0001), sP-selectin (p=0.01) and TATc (p=0.02) levels were higher in hypertensives compared to controls. Multivariate analysis including age, sex, risk factors, cardiovascular disease, anti-hypertensive treatment, sP-selectin and TATc showed that only sP-selectin was an independent predictor of VEGF (beta=0.40, p<0.03). Aspirin treated hypertensives showed a significant reduction of sP-selectin (-26%, p<0.01) and VEGF (-33%, p<0.01) levels. Moreover, the reduction of plasma VEGF levels directly correlated with that of sP-selectin (Rho=0.46, p=0.04). CONCLUSIONS: In vivo activation of platelets in hypertensive patients is responsible for enhanced circulating VEGF levels, which are significantly lowered by aspirin treatment.